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The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

Primary mucinous cystadenocarcinoma (MCA) is a rare breast carcinoma subtype showing overlapping histopathological features with mucinous cystadenocarcinoma of the ovary and pancreas. Current literature data suggest a favorable prognosis of breast MCAs despite its immunoprofile usually revealing lack of expression of estrogen receptor, progesterone receptor and HER-2 and high Ki67. As far as we know, only 36 cases have been reported in the literature to date. Its ambiguous morpho-phenotypic profile makes histological diagnosis very challenging. It must be distinguished from typical mucin-producing breast carcinomas and, above all, metastases from the same histotype in other sites (ovary, pancreas, appendix). Herein, we report the case of a primary breast MCA occurring in a 41-year-old female with peculiar histological features.

Herein, we present a clinicopathological and molecular analysis of four cases of endometrial carcinoma (EC) diffusely exhibiting dyshesive cells with wide eosinophilic and vacuolated cytoplasm (histiocyte-like tumor cells, HLTCs). We compared these HLTCs to similar cells found in microcystic, elongated and fragmented (MELF) pattern (n = 20) or after neoadjuvant chemotherapy (NAC) (n = 5). The four cases were endometrioid, serous, clear cell, and gastric-type; all were at FIGO stage ≥ III. HLTCs showed an epithelial Müllerian phenotype and at least focal CK20, HNF1β, and CK5/6 expression, with aberrant e-cadherin and β-catenin expression; two cases were MMR-deficient, and one was p53-abnormal; all were POLE wild type. MELF-associated and NAC-associated HLTCs showed similar morphological/immunophenotypical features. However, MELF-associated HLTCs were mainly intraglandular and inflammation-associated, did not form a distinct tumor component, and showed no relationship with lymph node metastases. In conclusion, different histotypes of EC may show a prominent HLTC component, which shows peculiar morphological/immunophenotypical features and appears associated with aggressive behavior.

Background The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature. Case presentation Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC. Conclusions In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.

The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of “simple” (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0–30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression (p < 0.001) and higher p16 expression (p < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs (p = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions.

Herein, we report a case of low-grade endometrial endometrioid carcinoma recurred on the vaginal stump, which showed a complete histotype shift toward a gastrointestinal-type carcinoma after chemotherapy. The recurrent tumor increased in volume during chemotherapy. Postchemotherapy histologic examination showed a pure mucinous signet-ring cell pattern with positivity for cytokeratin 20 and CDX2, focal SATB2 expression and negativity for cytokeratin 7 and estrogen and progesterone receptors. Such features led to consider a diagnosis of metastasis from a primary carcinoma of the gastrointestinal tract. The accurate exclusion of any primary lesions of gastrointestinal and of other sites allowed identifying the tumor as the recurrent endometrial carcinoma. Our case highlights that chemotherapy may induce a histotype shift from endometrioid carcinoma to gastrointestinal-type carcinoma; such occurrence might be a mechanism of resistance and might provide new insights on the sensitiveness of different histotypes to systemic therapies. Considering the possibility of a shift from endometrioid to gastrointestinal-type carcinoma may be useful for a correct diagnosis and an appropriate patient management.

Brain metastasis is a rare and generally late manifestation of an advanced-stage, high-grade serous ovarian carcinoma. Nowadays, the improved control of intra-abdominal disease by surgery and platinum-based chemotherapy results in a longer survival, allowing distant metastasis to implant and grow in the brain parenchyma. Herein, we describe a unique case of a cerebellar metastasis from clear cell ovarian carcinoma that initially presented as a FIGO Stage IC cancer. Surprisingly, 6 mo after surgery, the patient was in good condition with complete disappearance of symptoms and no evidence of recurrence. This relatively good biologic behavior may be explained by the presence of a PIK3CA-activating mutation in exon 9 which as previously reported in the literature, may be associated with better prognosis. To the best of our knowledge, this is the first reported case of cerebellar metastasis from ovarian clear cell carcinoma. In the presence of neurological symptoms, both clinicians and pathologists must be aware of this rare possibility, to assure correct patient management and effective therapeutic options. Generally, the prognosis of epithelial ovarian cancer patients with brain metastases is poor. PIK3CA mutations could be a good prognostic indicator in clear cell carcinomas.

Endometrial morular metaplasia (MorM) can show cytoplasm clarification, which may mimic clear cell carcinoma (CCC), especially on biopsy. We aimed to assess the expression of CCC markers in MorM.Twenty cases of MorM with areas of cytoplasmic clarification were assessed by immunohistochemistry for HNF1β, Napsin A, and P504S/alpha-Methylacyl-CoA racemase (AMACR); 60 tumors were selected as controls (20 classical MorM, 20 conventional squamous differentiation and 20 CCC).Eighteen cases (90%) showed overt squamous/keratinizing areas within MorM, and 11 cases (55%) showed isolated ghost cells which might mimic the hyaline globules of CCC. All cases (100%) showed expression of AMACR, which was mostly diffuse and strong; in all cases, the expression was restricted to the prototypical MorM areas, while glandular areas and overtly squamous areas were negative. Twelve cases (60%) showed HNF1β expression, which was focal/multifocal and/or weak; the expression was found in all tumor components. No case showed Napsin A expression in any component. Classical MorM showed similar immunophenotype, while conventional squamous differentiation did not show AMACR expression. Most CCC expressed AMACR (70%), HNF1β (85%), and Napsin A (75%), mostly with diffuse and strong positivity.MorM may show features that mimic CCC and consistently expresses AMACR, which may be accompanied by HNF1β expression; Napsin A is consistently negative instead. These findings should be considered to avoid overdiagnosis.

Integration between digital platforms and news organizations has produced a substantial platformization of news. This phenomenon has been accompanied by a growing political polarization of journalistic content, exacerbated in Italy by the high level of partisanship that traditionally characterizes the national media. This chapter outlines one part of a wider study on the debate about the regularization of migrant workers during the COVID-19 pandemic. The study, based on mixed methods and a two-level analytical approach, considers articles and posts published on Facebook by 12 different news providers (top-down) along with users' comments on this content (bottom-up). The authors here present the investigation into the coverage of migrant worker regularization by discussing the findings of the evaluative assertion and news frame analyses carried out on the selected articles and posts. Using this multidimensional approach, the study highlights the persistent nature of polarization within a highly fragmented public sphere.

In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in ≥10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in ≥10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p < 0.001) and multivariate analysis (p < 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement.

Background: Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients. Methods: A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words “cervical cancer”, “prognostic factors”, “pathology”, and “outcome” were used. Results: The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration. Conclusions: According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report.

As assessed by the recent data published by the Observatory “Okkio alla Salute” [1-2], the overweight and the obesity are increasingly common in childhood; in Italy, the 23% of kids of 8/9 years are overweighed and the 9% of them are obese. The diet therapy for the pediatric patient is increasingly necessary at local, outpatient and hospital level. The diet therapy and nutritional programmes, however, present some specific issues and complexities, from different points of view (biological and technical, behavioural and communication one). In this Paper, the Authors propose and analyse the approach to the child and its family context based on the Nutritional Counselling model. The Paper illustrates the theoretic principles and applicative practices of an approach based on a systemic view of the nutrition behaviour.

Neuroendocrine carcinoma (NEC) of the uterine cervix is less characterized than neuroendocrine neoplasms of other sites such as of the digestive system and the lung. Special AT-rich sequence-binding protein 2 (SATB2) recently emerged as a marker of well-differentiated neuroendocrine tumors of the lower gastrointestinal (GI) tract. Among NECs, SATB2 is more frequently expressed in cutaneous Merkel cell carcinoma than in NEC of other anatomical sites. In our study, we performed an immunohistochemical study of SATB2 in 16 NECs of the uterine cervix, where the expression of these markers is still undefined. SATB2 was expressed in 12/16 cervical NECs (75%), with 7/16 cases (44%) showing SATB2 positivity in ≥ 50% of cells. In 7 cervical NECs associated with a non-neuroendocrine component, the expression of SATB2 was restricted to the neuroendocrine component. SATB2 was positive in all cases that expressed CDX2 (n = 7) and TTF1 (n = 5), with no evident association with p16 and p53. Our study demonstrated that SATB2 is often expressed in NECs of the uterine cervix. This information should be taken into account when assessing the origin of a NEC.

BACKGROUND The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd), "TP53-mutated/p53-abnormal" (TP53mut/p53abn), and "no specific molecular profile" (NSMP). OBJECTIVE Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS). SEARCH STRATEGY Systematic review from January 2000 to January 2021. SELECTION CRITERIA Studies assessing the TCGA groups in UCS. DATA COLLECTION AND ANALYSIS Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P

Background: In the present study, we evaluated the prognostic value of TILs as well their relation with clinicopathological factors in patients affected by HER-2 positive breast cancer. Methods: We evaluated 47 patients with a histologically confirmed diagnosis of invasive breast carcinoma showing an immunohistochemically confirmed (score 3+) amplification of the c-erbB-2 gene for the presence of TILs and categorized in three predefined groups of low (0–10% immune cells in stromal tissue within the tumor), intermediate (11–40%), and high TILs (&gt, 40%). Results: Low, intermediate and high TILs were found in 17/47 (36%), 23/47 (49%) and 7/47(15%) cases, respectively. It was found that 6/47 cases treated with adjuvant chemotherapy plus trastuzumab underwent progression of the disease, none of these cases exhibited high TILs. It was found that 12/47 patients with a prognostically unfavorable stage of III and IV showed low and intermediate levels of TILs, while high TILs were never observed. A significant association between intermediate/high-levels of TILs, elevated KI 67 index and hormone receptors nuclear staining was observed. High concordance in TILs distribution was observed between preoperative breast biopsies and surgical samples. Conclusions: We observed a positive correlation between the TILs and the response to both adjuvant and neoadjuvant treatments in HER-2 positive BC. High TILs were also related to increased KI-67 index and to the expression of hormone receptors.

Background The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. Methods A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. Results Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. Conclusions The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

To investigate the expression of biological markers in primary vulvar Paget’s disease (VPD). Forty-one patients referred to a single major Center for Gynecologic Oncology from January 2008 to June 2018 were enrolled retrospectively: 30 non-invasive-VPD and 11 invasive-VPD. A total number of 60 samples, from all the 41 vulvar sites (VS), 8 metastatic lymph node sites (MLS) and 11 successive recurrent disease in vulvar site (RVS), were tested for an immunohistochemical panel, including the following markers: PD-L1, CD3, MSH2, MSH6, MLH1, PMS2, HER2/neu, EGFR, p16, p53, Ki67, ER, PR, AR, VEGF and CD31. We found a positive PD-L1 in 10% of non-invasive-VPD and 27% of invasive-VPD (18% VS; 38% MLS). ER and AR were expressed respectively in more than 70% and 75% of all specimens. HER2/neu amplification was found in 21% of non-invasive-VPD and 45% of invasive-VPD (40% VS; 38% MLS). A machine learning cluster analysis identified three groups among non- invasive-VPD: cluster-1 with higher median ER expression (40%); cluster-3 with more frequent HER2/neu overexpression (46%). Among invasive-VPD, two clusters were found: the second with more frequent HER2/neu overexpression (67% vs. 0%) and nodal metastases (100% vs. 25%). Repeating the IHC panel on the correspondent MLS and RVS, it significantly changed, respectively, in 50% and 27%. This study reveals the expression of PDL-1 and ER and confirms the expression of HER2/AR in VPD; new bases are provided to design multicenter clinical trials on personalized target therapies.

Background Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. Methods Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value Results Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. Conclusions In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

Introduction In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. Objective To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value Results Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. Conclusion MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.

Simple Summary Histopathological classification of endometrial carcinoma has evidenced two main groups with different biological behavior: low-grade (G1–G2) and high-grade (G3) endometrial tumors. Moreover, the Cancer Genome Atlas (TCGA) documented four molecular categories with distinct clinical, pathologic, and molecular features: POLE/ultramutated (7% of cases) microsatellite instability (MSI)/hypermutated (28%), copy-number low/endometrioid (39%), and copy-number high/serous-like (26%). The aim of the present paper is to review all endometrial carcinoma histotypes in light of the morphological and molecular prognostic TCGA groups. Abstract Endometrial carcinoma represents the most common gynecological cancer in Europe and the USA. Histopathological classification based on tumor morphology and tumor grade has played a crucial role in the management of endometrial carcinoma, allowing a prognostic stratification into distinct risk categories, and guiding surgical and adjuvant therapy. In 2013, The Cancer Genome Atlas (TCGA) Research Network reported a large scale molecular analysis of 373 endometrial carcinomas which demonstrated four categories with distinct clinical, pathologic, and molecular features: POLE/ultramutated (7% of cases) microsatellite instability (MSI)/hypermutated (28%), copy-number low/endometrioid (39%), and copy-number high/serous-like (26%). In the present article, we report a detailed histological and molecular review of all endometrial carcinoma histotypes in light of the current ESGO/ESTRO/ESP guidelines. In particular, we focus on the distribution and prognostic value of the TCGA groups in each histotype.

Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms, we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. Methods: Consultation cases covering a 5-year period (2016–2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA, Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA, Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. Results: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. Conclusions: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results.

Background: The diagnostic role of Wilms’ tumor 1 (WT1) is well known in gynaeco-pathological setting, since it is considered a specific marker of serous histotype and adnexal origin. Moreover, its oncogenic role has been recently highlighted in many cancers and it has also been regarded as a promising target antigen for cancer immunotherapy. However, the relationship between its expression and prognostic role in uterine cancer remains unclear. We analyzed the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma by completing a search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the PICOS (Participants, Intervention, Comparison, Outcomes, Study Design) model through PubMed, Scopus and Web of Science databases to identify studies that fit our search criteria. The objective of the current meta-analysis was to investigate the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma. Materials and Methods: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to April 2020. Studies were considered eligible if they evaluated the WT1 expression in uterine carcinoma. Results: In total, 35 articles were identified that used uterine carcinoma criteria and provided data for 1616 patients. The overall rate of WT1 expression in uterine carcinoma was 25%. The subgroup analysis of uterine cancer types revealed that WT1 was expressed differently among different histotypes (endometrioid, clear cell, serous carcinoma and carcinosarcoma). Discussion and Conclusions: The WT1 immunohistochemical expression is not limited to serous histotype and/or ovarian origin. In fact, a significant proportion of endometrial adenocarcinomas can also show WT1 immunoreactivity. Moreover, our study suggests that WT1 may be a potential marker to predict the prognosis of patients with uterine cancer, but more studies are needed to confirm its role in clinical practice.

ObjectiveWe compared ultrastaging and one-step nucleic acid amplification (OSNA) examination of sentinel lymph nodes in two homogeneous patient populations diagnosed with early stage cervical cancer. The primary aim of our study was to evaluate the rate and type of sentinel lymph node metastases detected by ultrastaging and OSNA assay. Secondary aims were to define the sensitivity and the negative predictive value of sentinel lymph node biopsy assessed with OSNA and ultrastaging and to define the role of sentinel lymph node assessment in predicting non-sentinel lymph node status.MethodsConsecutive patients who underwent surgery (radical hysterectomy or trachelectomy or cervical conization) at our institution, between January 2018 and March 2020, were enrolled. All patients had a preoperative diagnosis of early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) 2018 stages IA–IIB) and underwent sentinel lymph node assessment with ultrastaging or OSNA. Patients with advanced FIGO stages and special histology subtypes (other than squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) or patients with sentinel lymph nodes analyzed only with hematoxylin and eosin were excluded. Clinical data were compared using the χ2 test and Fisher’s exact test. A κ coefficient was determined with respect to lymph node assessment. A p value ResultsA total of 116 patients were included in this retrospective analysis (53 ultrastaging, 63 OSNA). Overall, 531 and 605 lymph nodes were removed in the ultrastaging and OSNA groups, respectively, and 140 and 129 sentinel lymph nodes were analyzed in the ultrastaging and OSNA groups, respectively. 22 patients had metastatic sentinel lymph nodes: 6 (11.3%) of 53 patients in the ultrastaging group and 16 (25.4%) of 63 patients in the OSNA group. The total amount of positive SLNs was 7 (5%) of 140 in the ultrastaging group and 21 (16.3%) of 129 in the OSNA group, respectively (p=0.0047). Pelvic lymphadenectomy was performed in 26 (49.1%) of 53 patients in the ultrastaging group and in 34 (54%) of 63 patients in the OSNA group due to comorbidities. Metastatic non-sentinel lymph nodes were found in 4 patients: 2 (7.7%) of 26 patients in the ultrastaging group and 2 (5.9%) of 34 patients in the OSNA group, respectively. The total amount of positive pelvic lymph nodes was 3 (0.6%) of 531 in the ultrastaging group and 4 (0.7%) of 605 in the OSNA group (p=0.61). In the OSNA group, only 2 patients with negative sentinel lymph nodes had metastatic disease in the pelvic lymph nodes. By contrast, no patients with OSNA-positive sentinel lymph nodes had metastases in the pelvic lymph nodes. In the ultrastaging group, all patients with negative sentinel lymph nodes did not have metastatic disease in other pelvic lymph nodes.ConclusionsOSNA assessment of sentinel lymph nodes was associated with a negative predictive value of 91% but poor reliability in detecting node metastases in non-sentinel pelvic lymph nodes. Of note, the ultrastaging protocol revealed higher sensitivity and more reliability in predicting pelvic non-sentinel lymph node status.

Summary Up to now, Italy is one of the European centers with the most active Coronavirus cases with 233,836 positive cases and 33,601 total deaths as of June 3rd. During this pandemic and dramatic emergency, Italian hospitals had also to face neoplastic pathologies, that still afflict the Italian population, requiring urgent surgical and oncological treatment. In our Cancer Center Hospital, the high volume of surgical procedures have demanded an equally high volume of intraoperative pathological examinations, but also posed an additional major challenge for the safety of the staff involved. The current commentary reports our experience in the past two months (since March 9th) for a total of 1271 frozen exams from 893 suspect COVID-19 patients (31 confirmed).

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2&ndash, 2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell&ndash, neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell&ndash, neuroendocrine carcinomas, LCNECs), in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers, p16 was intensely expressed in 14 (87.5%) cases, SST5 in 11 (56.25%, score 2&ndash, 3, in 9 cases), SST2 in 8 (50%, score 2&ndash, 3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC, however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.

Aims Microcystic, elongated, and fragmented (MELF) pattern of myoinvasion has been related with increased risk of lympho-vascular space invasion (LVSI) and lymph node metastasis. We analysed a cohort of endometrioid endometrial carcinomas (EECs) to examine the relationships between the MELF pattern of invasion and the clinico-pathological and immunohistochemical features of EEC. Methods and results 129 EECs were evaluated for the presence of MELF pattern and immunohistochemically tested for Mismatch repair (MMR) proteins, p16, p53 and beta-catenin. We observed 28 MELF + EECs and 101 MELF- EECs. LVSI was observed in 20 MELF + cases and in MELF- tumors. Lymph-node metastases were observed in 7 MELF + cases (2 macrometastases, 3 micrometastases and 2 ITCs). None of the MELF- cases showed micrometastases or ITCs, 18 cases had macrometastatic lymph-nodes. Statistical analysis showed that MELF + tumors carry an increased risk of developing nodal metastasis independent of tumor dimension and LVSI. Loss of MMR proteins expression was observed in 11 MELF + cases and 45 MELF- cases, respectively. Our data showed a higher frequency of immunohistochemical MLH1-PMS2 loss in MELF- pattern of invasion (32.67% of MELF- cases vs 21.43% of MELF + cases) but a higher prevalence of MSH2-MSH6 loss in MELF + pattern (7.14% in MELF + population vs 3.96% of MELF- population) Conclusions The morphological recognition of MELF pattern is more reliable than immunohistochemical and molecular signatures of EEC in predicting the risk of nodal involvement. The observed higher prevalence of MSH2-MSH6 loss in MELF + group and MLH1-PMS2 loss in MELF- group may suggest a different molecular signature.